Molecular pathways: Isocitrate dehydrogenase mutations in cancer

170Citations
Citations of this article
222Readers
Mendeley users who have this article in their library.

Abstract

IDH1 and IDH2 are homodimeric enzymes that catalyze the conversion of isocitrate to α-ketoglutarate (α-KG) and concomitantly produce reduced NADPH from NADP. Mutations in the genes encoding IDH1 and IDH2 have recently been found in a variety of human cancers, most commonly glioma, acute myeloid leukemia (AML), chondrosarcoma, and intrahepatic cholangiocarcinoma. The mutant protein loses its normal enzymatic activity and gains a new ability to produce the "oncometabolite" R(-)-2- hydroxyglutarate (R-2-HG). R-2-HG competitively inhibits α-KG-dependent enzymes which play crucial roles in gene regulation and tissue homeostasis. Expression of mutant IDH impairs cellular differentiation in various cell lineages and promotes tumor development in cooperation with other cancer genes. First-generation inhibitors of mutant IDH have entered clinical trials, and have shown encouraging results in patients with IDH-mutant AML. This article summarizes recent progress in our understanding of the role of mutant IDH in tumorigenesis.

Cite

CITATION STYLE

APA

Clark, O., Yen, K., & Mellinghoff, I. K. (2016). Molecular pathways: Isocitrate dehydrogenase mutations in cancer. Clinical Cancer Research, 22(8), 1837–1842. https://doi.org/10.1158/1078-0432.CCR-13-1333

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free